The concomitant use of calcineurin inhibitors (CNIs) with mTOR inhibitors, that is, either sirolimus (SRL) or everolimus (ERL), in de novo renal transplant patients is still debated. Prescription of full doses of cyclosporine A (CsA) with either SRL or ERL in that population leads to impaired renal function and hyperlipidemia compared with a regimen using mycophenolate mofetil (MMF) with CsA. The current data for the use of SRL doses, ranging from 0.5 to 2 mg/d, or SRL troughs ranging from 8 to 12 ng/mL with conventional doses of tacrolimus, are associated with reduced renal function, higher blood pressure, and an increase in serum lipids compared with MMF/tacrolimus therapy.